2025-03-01 東邦大学,名古屋大学,科学技術振興機構
<関連情報>
- https://www.toho-u.ac.jp/press/2024_index/20250301-1454.html
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00123-8
セプチン3は記憶とL-LTP依存的な小胞体のスパインへの伸展を制御する Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines
Natsumi Ageta-Ishihara∙ Yugo Fukazawa∙ Fumiko Arima-Yoshida∙ … ∙ Kaoru Inokuchi∙ Haruhiko Bito ∙ Makoto Kinoshita
Cell Reports Published:February 28, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.115352
Graphical abstract
Highlights
- L-LTP accompanies cytoskeletal remodeling that involves the septin subunit SEPT3
- L-LTP causes smooth ER (sER) extension into spines via SEPT3-myosin-Va interaction
- Spine sER confers greater Ca2+ responses, enhancing local synaptic activity
- Sept3-/- mice show scarce sER spines and reduced long-term spatial/object memory
Summary
Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca2+ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3-/-) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.
